Endocrine cells have the ability to concentrate and store hormones into a secretory granule and release the contents of the secretory granule on stimulation. Endocrine cells have, therefore, three properties not shared by many other cell types, the capacity to segregate hormones from other proteins, to concentrate them and to regulate fusion with the plasma membrane. Recent data from several labs, including our own, have generated a detailed model of how sorting, concentration and secretion occur. We have generated a permeabilized cell preparation from the rat pheochromocytoma cell line, PC12, that allows us to examine how immature secretory granules pinch-off from the trans Golgi network, how they mature, how they interact with the cytoskeleton, and how their exocytosis is regulated. We can learn from such in vitro studies if there is cell type-specific sorting machinery in regulated secretory cells. The steps in secretory granule maturation seen in in vitro studies are consistent with the steps in mucocyst maturation observed in mutants of Tetrahymena thermophila, a ciliated protozoan in which secretion-defective mutants are readily available. Analysis of membrane traffic in endoplasmic reticulum and Golgi complex cells has profited enormously from the interaction between in vitro reconstitution of mammalian cell traffic and the genetic defects in membrane traffic in yeast. The similarities we have observed between regulated secretion in Tetrahymena and endocrine cells suggest that study of one will help illuminate the properties of the other. With these two approaches we hope to generate definitive molecular information on regulation secretion.